The efficacy of oral anticoagulation (OAC) for stroke prevention in patients with nonrheumatic atrial fibrillation (AF) has clearly been established. However, a substantial number of patients with AF who are at high risk for thromboembolic events are not candidates for long-term OAC. The left atrial appendix (LAA) is the most common place of thrombosis in patients with AF, and it can easily be excluded from the systemic circulation at the time of cardiac surgery by excision, ligation, suturing, or stapling. Currently, removal of the LAA at the time of mitral valve surgery is recommended to reduce future stroke risk. The ongoing LAA Occlusion Study (LAAOS) is evaluating the efficacy of the routine LAA occlusion in patients undergoing elective coronary artery bypass graft surgery. Recently, two devices specifically designed for percutaneous transcatheter LAA occlusion have been introduced: the Percutaneous LAA Transcatheter Occlusion (PLAATO; Appriva Medical Inc) and WATCHMAN LAA system (Atritech, Inc). More than 200 PLAATO devices were implanted worldwide in patients with nonrheumatic AF who were at high risk for ischemic stroke and not candidates for long-term OAC. In a follow-up time of 258 patient-years, an estimated 61% reduction in stroke risk was achieved with PLAATO procedure. The WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation (PROTECT AF) study was designed to demonstrate the safety and efficacy of the WATCHMAN device in patients with nonvalvular AF who are eligible for long-term OAC. The trial is assessing whether the treatment arm (WATCHMAN device) is noninferior to the control arm (warfarin). Although present results suggest that LAA occlusion may reduce the long-term stroke risk, available data are still very limited. At present, percutaneous LAA occlusion may be an acceptable option in selected high-risk patients with AF who are not candidates for OAC. The current understanding of LAA exclusion for the prevention of stroke in patients with nonrheumatic AF is the major focus of this review.